Genetic diseases have a wide spectrum of presentations ranging from mild in individuals unaware of their condition to severe, resulting in death at a young age. Single-gene disorders are caused by mutations that affect individual genes. Examples include cystic fibrosis or sickle cell anemia. Chromosomal disorders such as Down syndrome are caused by changes in the number or structure of chromosomes. Multifactorial disorders result from interactions between genes and environment and include common diseases such as congenital birth defects or cancer. Single-gene and chromosomal disorders are much less common than multifactorial diseases, but their recurrence risk is often higher.
Family History as a Sign for Genetic Disorders
A family history documenting that a disease runs through the family is the single most useful indicator that a condition might be genetic. For example, Marfan syndrome appears in multiple successive generations, equally affecting males and females. In contrast, many inborn errors of metabolism may affect only one generation and present in young infants or children. They may be more common in certain ethnic groups and in children from blood-related parents.
Cancer as Sign of Genetic Disease
Hereditary cancer syndromes occur in individuals carrying a cancer-predisposing genetic mutation. Although uncommon, they are important to recognize because they confer a high lifetime risk of cancer affecting family members who inherit the cancer-predisposing genetic mutation. Characteristics of hereditary cancer syndromes are two or more relatives with cancer, cancer in a family member under 50 years of age, the same type of cancer in several family members, more than one type of cancer in
Genetic Red Flags
A red flag is any sign that suggests the presence of a genetic disorder and that may require further action. The mnemonic "GENES" summarizes the most important signs to recognize genetic disorders: G -- Groups of congenital anomalies or multiple birth defects; E -- Exceptional presentation of common conditions, which may include early onset of disease or unusually severe reaction to infectious or metabolic stress; N -- Neurodevelopmental delay or regression; E -- Exceptional pathology such as rare tumors multiple primary cancers; and S -- Surprising laboratory values.
Checklist for Children
Characteristics that may indicate the presence of genetic defects in children include birth defects such as congenital heart disease or cleft lip and palate. Children may present with failure to thrive, developmental delay, deafness or blindness. An unusual physical appearance may include unusually shaped ears, different-colored or wide-spaced eyes, facial symmetry, white patch of hair, excessive skin or many birth marks. Skeletal abnormalities such as tall or short stature, extra or missing digits, or webbing between the fingers or toes are commonly found in genetic syndromes.
Checklist for Adults
Some genetic syndromes may not manifest or be recognized until adulthood. Features include hearing loss, visual loss, mental retardation or mental illness, and seizures. Clues from previous pregnancies are previous children with birth defects or learning delays, more than two miscarriages, stillbirths and unexplained infertility. These are only general guidelines that need to be evaluated on an individual basis since some of these features are found in the general population or may be confused with other medical problems. Always consult a physician for more information.
References
- OMIM: Online Mendelian Inheritance in Man
- American Journal of Human Genetics: Genetic Disorders in Children and Young Adults: a Population Study
- CA, A Cancer Journal for Clinicians: Identifying and Testing for Hereditary Susceptibility to Common Cancers
- "Primary Care: Clinics in Office Practice;" Genetic red flags: clues to thinking genetically in primary care practice; Whelan AJ, Ball S, Best L et al.; 2004
- GeneReviews: Who Should Have a Genetics Consultation?
